ENST00000420251.5:n.438-4T>C

Variant names:

• chr6-30035987-A-G
• rs3869066
• ENST00000420251.5:n.438-4T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000420251.5(POLR1HASP):​n.438-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 456,638 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (71 hom., cov: 32)
  • Exomes 𝑓: 0.031 (305 hom.)
• Consequence: POLR1HASP ENST00000420251.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 9 publications found

Genes affected

POLR1HASP (HGNC:):

POLR1HASP (HGNC:13924): (POLR1H antisense, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1HASP	NR_026751.2	n.443-4T>C		splice_region_variant, intron_variant	Intron 3 of 5
POLR1HASP	NR_145416.1	n.443-4T>C		splice_region_variant, intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1HASP	ENST00000420251.5	n.438-4T>C		splice_region_variant, intron_variant	Intron 3 of 5	1
POLR1HASP	ENST00000437417.5	n.977-4T>C		splice_region_variant, intron_variant	Intron 2 of 5	1
POLR1HASP	ENST00000376797.7	n.260-4T>C		splice_region_variant, intron_variant	Intron 2 of 11	2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3357 AN: 152224 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.00719

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.0376 AC: 5144 AN: 136902 AF XY: 0.0344

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.0244

Gnomad FIN exome AF: 0.0166

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0320

GnomAD4 exome AF: 0.0310 AC: 9436 AN: 304296 Hom.: 305 Cov.: 0 AF XY: 0.0291 AC XY: 5048 AN XY: 173280

African (AFR) AF: 0.00556 AC: 48 AN: 8626

American (AMR) AF: 0.109 AC: 2963 AN: 27254

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 236 AN: 10790

East Asian (EAS) AF: 0.0334 AC: 307 AN: 9204

South Asian (SAS) AF: 0.0276 AC: 1650 AN: 59732

European-Finnish (FIN) AF: 0.0181 AC: 232 AN: 12788

Middle Eastern (MID) AF: 0.0119 AC: 33 AN: 2780

European-Non Finnish (NFE) AF: 0.0226 AC: 3593 AN: 158888

Other (OTH) AF: 0.0263 AC: 374 AN: 14234

GnomAD4 genome AF: 0.0221 AC: 3365 AN: 152342 Hom.: 71 Cov.: 32 AF XY: 0.0221 AC XY: 1643 AN XY: 74504

African (AFR) AF: 0.00717 AC: 298 AN: 41576

American (AMR) AF: 0.0597 AC: 914 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.0316 AC: 164 AN: 5186

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4828

European-Finnish (FIN) AF: 0.0158 AC: 168 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1587 AN: 68034

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0261 Hom.: 187

Bravo AF: 0.0267

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3869066; hg19: chr6-30003764;